In patients taking ACE-inhibitors, the blunted production of angiotensin II and the consequent reduced stimulation of AT1- and AT2 receptor may induce an escape phenomenon, which consists in the accumulation of angiotensin I and production of angiotensin II through alternative synthetic bio-pathways (cathepsine C, chimases).10 This phenomenon, well described in patients with congestive heart failure, may be prognostically important.

In the kidneys, especially at the renal tubular level, the stimulation of AT2 could mediate natriuresis which could also contribute to the antihypertensive effect.26,27 Stopping valsartan intake is not associated with rebound of the BP level.